Honey has been used for centuries by cultures through the world for its multiple health benefits. Two of the most important health benefits of honey are its anti-bacterial and anti-inflammatory properties. Manuka honey, which is produced by bees that collect nectar from Leptospermum scoparium, a plant native to New Zealand and southern Australia, has been identified as being a variety of honey that exhibits particularly effective anti-bacterial and anti-inflammatory properties. Jelly Bush honey, which is produced by bees that collect nectar from Leptospermum polygalifolium, a plant native to Australia, has also been identified as being a variety of honey that exhibits particularly effective anti-bacterial and anti-inflammatory properties.
Recently, it was discovered that the chemical, methylglyoxal (MGO, also called 2-oxopropanal and pyruvaldehyde), is a major component of the antibacterial activity of Leptospermum derived honey, such as manuka honey and jelly bush honey. Manuka honey and jelly bush honey samples contain greater concentrations of MGO, and have a higher amount of anti-bacterial activity as compared to honey samples with lower concentrations of MGO. MGO is believed to confer anti-bacterial properties on honey because MGO is a highly chemically reactive compound, and MGO can readily react with cellular molecules. The chemical reactions between MGO and cellular molecules in bacteria damage bacterial molecules that are important for viability. In this way, MGO functions as an antibacterial agent.
The presence of high levels of MGO in the honey is a feature that distinguishes manuka honey and jelly bush honey from other varieties of honey. While most varieties of honey exhibit some anti-bacterial activity, the anti-bacterial activity in most varieties of honey is primarily a result of the presence of hydrogen peroxide in the honey. Leptospermum derived honey, in contrast, exhibits anti-bacterial activity primarily because of the presence of MGO in the honey.
In 2004, Kohno et. al. examined the anti-inflammatory effects or actions of royal jelly at a cytokine level. The results suggest that royal jelly has anti-inflammatory actions brought about by an inhibition of pro-inflammatory cytokine production, such as TNF-α, IL-6 and IL-1, by activated macrophages. The study further suggests that the active fractions or components from the royal jelly extracts are sized between 5 kDa and 30 kDa. Thus, most honeys may have a weak anti-inflammatory effect due to royal jelly proteins that occur in the honey.
While multiple mechanisms of action of the anti-bacterial activity of manuka honey have been elucidated, the mechanisms whereby manuka honey functions as an anti-inflammatory agent have remained unknown. There is a need to develop anti-inflammatory agents based on honey, as many anti-inflammatory agents currently available have major drawbacks to their use. For example, COX-2 inhibitors, a form of non-steroidal anti-inflammatory drug (NSAID), may increase the risk of heart attack and stroke in patients, and aspirin may increase the risk of gastrointestinal bleeding. Additionally, corticosteroids are reported to inhibit the growth of epithelial cells and NSAIDs are reported as being cytotoxic so both of these classes of anti-inflammatory agents are unsuitable for use in wound care. Anti-inflammatory agents derived from honey may have fewer toxic side effects in one or more areas than drugs currently available, and may also offer different possible uses than anti-inflammatory drugs currently available.
Described in the co-pending application PCT/NZ/2011/000271 is a modified apalbumin of approximately 55-75 kDa from manuka honey that results from the high levels of methylglyoxal found in manuka honey. The inventors have identified that the modified apalbumin or major royal jelly protein has significantly greater anti-inflammatory properties than an unmodified apalbumin or major royal jelly protein.